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Company: Merck
Catalog#: 345789
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Protocols to Study Declarative Memory Formation in Mice and Humans: Optogenetics and Translational Behavioral Approaches
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2018-06-20
[Abstract]  Declarative memory formation depends on the hippocampus and declines in aging. Two functions of the hippocampus, temporal binding and relational organization (Rawlins and Tsaltas, 1983; Eichenbaum et al., 1992; Cohen et al., 1997), are known to decline in aging (Leal and Yassa, 2015). However, in the literature distinct procedures have been used to study these two functions. Here, we describe the experimental procedures used to investigate how these two processes are related in the formation of declarative memory and how they are compromised in aging (Sellami et al., 2017). First, we studied temporal binding using a one-trial learning procedure: trace fear conditioning. It is classical Pavlovian conditioning requiring temporal binding since a brief temporal gap ... [摘要]  陈述性记忆的形成取决于海马体和老化程度的下降。已知海马,时间结合和关系组织的两种功能(Rawlins和Tsaltas,1983; Eichenbaum等人,1992; Cohen等人,1997),已知老龄化下降(Leal和Yassa,2015)。但是,在文献中已经使用不同的程序来研究这两个功能。在这里,我们描述了用于研究这两个过程如何与陈述性记忆的形成以及它们如何在衰老中受到损害有关的实验程序(Sellami et。,2017)。首先,我们使用单一试验性学习程序研究了时间绑定:追踪恐惧条件反射。这是经典的巴甫洛夫条件需要时间约束,因为短暂的时间间隔将条件刺激(CS)和无条件刺激(US)呈现分开。我们将追踪恐惧条件程序与光遗传学方法相结合,并且我们表明时间依赖性依赖于背侧(d)CA1活性在时间间隙上的依赖性。然后,我们研究了时间绑定和关系组织之间在声明性记忆形成中的相互作用,这种相互作用使用了小鼠中的两阶段径向迷宫任务及其在人类中的虚拟类比。行为过程包括一个初始学习阶段,在这个阶段中,受试者获得每个手臂持续的奖励/无奖赏价值,然后是测试阶段,其中武器中的奖励突发事件保持不变,但武器重新组合以评估灵活性,陈述性记忆。我们证明了dCA1依赖的时间结合对于记忆的关系组织的发展是必需的,这允许灵活的陈述记忆表达。此外,在衰老过程中,陈述性记忆的退化是由于时间约束能力的减少而阻碍了关系组织。 ...

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